Compositions comprising a combination of a free sphingoid base and a ceramide and uses thereof

ABSTRACT

The present invention discloses a composition for topical use comprising a free sphingoid base and a ceramide. The compositions of the invention are suitable for application to skin conditions associated with an impaired barrier function, in particular to skin conditions further associated with a deranged regulation of cell growth and differentiation, an inflammatory condition and/or an infectious state

FIELD OF THE INVENTION

[0001] The present invention relates to the field of topical use ofcompositions comprising a selected combination of sphingolipids.

BACKGROUND OF THE INVENTION

[0002] The human skin forms a structural and adapted barrier to theenvironment. It further plays an important physiological role since itprovides not only protection and thermoregulation, but also has ametabolic and sensorial function and storage capacity.

[0003] It has been shown that the lipid composition of the epidermalcells within the skin changes considerably when the cells migrate to theouter surface and differentiate. The cells in the basal layer contain acomplex lipid composition, with phospholipids as the major constituent.In the granular layer the phospholipid content is diminished while theamount of cerebrosides (glycosylceramides), ceramides, cholesterol andcholesterol sulphate is increased as result of de novo synthesis andstorage into the so-called lamellar bodies. In the outermost lipid layerof the epidermis, called the stratum corneum (horny layer) thephospholipids and cerebrosides have vanished completely. The mostabundant lipids in this layer are ceramides, which mainly have beenformed by enzymatic deglycosylation of cerebrosides.

[0004] The barrier function of the skin mainly is provided by thestratum corneum. The stratum corneum consists of corneocytes embedded inan extracellular matrix of multiple bilayers of lipids. Theintercellular lipid phase of the stratum corneum has roughly thefollowing composition: 40% ceramides, 25% cholesterol, 10% cholesterylsulphate and 25% free fatty acids. As long as the “bricks and mortar”construction of the stratum corneum is not affected, the skin isprovided with both a perfect protective layer and a filter-activepermeability layer.

[0005] Several categories of skin conditions or disorders are knownwhich are characterized by an impaired lipid barrier function, furtheraccompanied by characteristics like a deranged regulation of cell growthand differentiation (e.g. hyperproliferation and/or decreaseddifferentiation of keratinocytes, decreased desquamation ofcorneocytes), an imflammatory response and/or an infectious state. Inthese skin conditions, the skin generally displays a rough, red, dry,chapped and/or swollen character. Typical examples of such disorders arexerosis, acne vulgaris, psoriasis, atopic dermatitis, contactdermatitis, UV-induced erythema, and the like.

[0006] Satisfactory treatment methods for these disorders presently arenot available. Emollient creams and lotions may relieve part of thesymptoms, but often only temporarily. Conventional antiimflammatorycreams, of which corticosteroid creams form the main part, are moreeffective for the treatment of certain disorders but continued use mayreduce the effectiveness of the treatment and/or may give sidereactions. In addition, conventional antiinflammatory as well asantimicrobial creams typically are not adapted to restore an impairedbarrier function.

[0007] Ceramides are generally applied in cosmetics because of theirmoisture-retaining properties (see for instance Japanese patentapplication J61-260008).

[0008] In International patent application WO94/00127 it has beendescribed that formulations containing specific lipid mixtures should beapplied for an optimal treatment of skin disorders associated with adisrupted epidermal barrier. Said lipid mixtures comprise lipidsselected from the three major classes of naturally-occurring epidermallipids, i.e. the classes of ceramides, cholesterol and free fatty acids.However, in order to be optimally effective for skin conditionsassociated with inflammatory or infectious phenomena, these formulationshave to be applied together with conventionally used therapeutic agents.

[0009] Surprisingly, it is shown by the present invention that topicalcompositions comprising a combination of a free sphingoid base and aceramide have a beneficial effect when applied on skin conditionsassociated with an impaired barrier function, and especially whenapplied on skin conditions further associated with a deranged regulationof cell growth and differentiation, inflammatory and/or infectiousphenomena.

DESCRIPTION OF THE INVENTION

[0010] The present invention discloses compositions suitable for topicaluse comprising a combination of a free sphingoid base and a ceramide.The topical compositions of the invention can be cosmetic as well asdermatologic compositions.

[0011] It is shown by the present invention that topical compositionscomprising a combination of a free sphingoid base and a ceramide have apositive and beneficial effect on skin conditions associated with animpaired lipid barrier function. The synergistic effects of thecombination of a free sphingoid base and a ceramide become even moreapparent when the compositions according to the invention are used forthe treatment of skin conditions wherein an impaired lipid barrierfunction further is associated with a deranged regulation of cell growthand differentiation, an imflammatory condition and/or an infectiousstate. Said deranged regulation of cell growth and differentiation ischaracterized by conditions like hyperproliferation of keratinocytes,decreased differentiation of keratinocytes and/or decreased desquamationof corneocytes.

[0012] The present invention shows that the presence of a free sphingoidbase especially improves the efficacy of the composition of theinvention with regard to its antiinflammatory and/or its antimicrobialactivity. It is shown that this efficacy improvement is due to, inparticular, an antimicrobial and antiinflammatory activity of the freesphingoid base.

[0013] The free sphingoid base present in the composition according tothe invention has a general structure according to Formula 1:

[0014] wherein:

[0015] A is CH₂—CH₂, CH═CH or C(H)OH—CH₂, and

[0016] R is a straight chain or branched alkyl group having 10 to 22carbon atoms which may optionally contain one or more double bondsand/or may optionally be substituted with one or more hydroxyl groups,preferably is a straight chain alkyl group having 12 to 18 carbon atoms,more preferably is a straight chain alkyl group having 13 carbon atoms.

[0017] The ceramide present in the composition according to theinvention has a general structure according to Formula 2:

[0018] wherein:

[0019] A and R are defined as above, and

[0020] R′ is a straight chain or branched alkyl group having 13 to 55carbon atoms, preferably 15 to 50 carbon atoms, more preferably 17 to 44carbon atoms; the alkyl chain may optionally be interrupted by an oxygenatom or by an internal ester group; may optionally contain one or moredouble bonds; and may optionally be substituted with one or morehydroxyl groups.

[0021] The free sphingoid base which is present in the composition ofthe invention preferably is a sphingosine, a sphinganine or aphytosphingosine. More preferably, the free sphingoid base is aphytosphingosine obtainable by deacetylation oftetraacetylphytosphingosine obtainable by fermentation of the yeastPichia ciferri.

[0022] The ceramide which is present in the composition of the inventioncan be extracted from a natural source, for instance a mammalian source,or can be obtained via synthetic means. An example of a suitablechemical synthesis method is the acylation of a free sphingoid base witha suitable fatty acid, for instance via the acylation method asdisclosed in international patent application WO93/20038.

[0023] In a preferred embodiment of the invention, the ceramide presentin the composition of the invention is a ceramide which corresponds instereochemical configuration to a ceramide isolatable from mammalianskin. Ceramides as isolated from mammalian skin typically can besubdivided in six heterogeneous classes of compounds, ceramide 1, 2, 3,4, 5, 6I and 6II. In general, these ceramides consist of a freesphingoid base in amide linkage with a nonhydroxy or an α-hydroxy fattyacid, or an ω-hydroxy fatty acid esterified with an additional fattyacid. A ceramide which corresponds in stereochemical configuration to amammalian skin ceramide may for instance be obtained by acylation ofPichia ciferri-derived phytosphingosine. Examples of such ceramides arethe ceramides disclosed in international patent applications WO93/20038,WO95/11881, WO95/25716 and WO96/10557.

[0024] Within the context of the present invention, an individualceramide as well as a mixture of two or more different ceramides can beapplied in a topical composition.

[0025] In that regard, said mixture of two or more different ceramidesmay include various ceramide combinations, the choice of a specificcombination depending among others on the desired application.

[0026] A combination of two or more representatives of each ceramideclass may for instance be applied, since said combination may lead to anincreased ceramide solubility in the composition according to theinvention. Individual ceramides may tend to crystallize and consequentlybecome inert and unfunctional.

[0027] A further option is a combination of, on the one hand, asphinganine- and/or sphingosine-containing ceramide and, on the otherhand, a phytosphingosine-containing ceramide (e.g. ceramide 1 and/or 2and/or 4/5 with ceramide 3 and/or Ceramide 6). Such a combinationconsists of two types of ceramides having a head group which differs inhydrophilicity and this may increase barrier enhancing properties of thesame.

[0028] For the same reason, a combination is feasible of a ceramidecontaining an α-hydroxy fatty acid with a ceramide containing anon-hydroxylated fatty acid (e.g. ceramide 1 and/or ceramide 2 and/orceramide 3 with ceramide 4/5 and/or ceramide 6).

[0029] Further feasible is a combination of a ceramide containing amedium chain fatty acyl group of 16 to 22 carbon atoms with a ceramidecontaining a long chain fatty acyl groups of 22 to 32 carbon atoms,since such a combination naturally occurs in the stratum corneum and mayalso be important for a stronger barrier structure (Bouwstra et al.(1996), J. Lipid Res. 37, 999-1011).

[0030] The composition of the invention optionally may comprise one ormore additional skin lipid compounds, such as cholesterol, cholesterolesters like cholesteryl sulphate, free fatty acids like palmitic,stearic, behenic, oleic and/or linoleic acid and/or other sphingolipidslike glycoceramides. The composition of the invention may furthercomprise ceramide compounds having a short-chain acyl group, said shortchain acyl group optionally being α-hydroxylated (so-called short-chainceramides).

[0031] With respect to glycoceramides, two groups of these compounds aretypically distinguished, i.e. cerebrosides and gangliosides. Acerebroside is understood to be a glycoceramide wherein amonosaccharide, mostly glucose or galactose, is attached to the oxygenof the —CH₂OH group of the ceramide according to Formula 2. Ingangliosides oligosaccharides, frequently including sialic acid, areattached to the same.

[0032] With respect to short-chain ceramides, a short chain acyl groupis meant to comprise acyl groups having 2 to 14 carbon atoms. Apreferred ceramide with a short-chain acyl group isacetylphytosphingosine. Examples of ceramides having a short-chainα-hydroxyacyl group are disclosed in international patent applicationWO95/29151.

[0033] In one embodiment of the invention, a composition comprising afree sphingoid base and a ceramide may contain as the sole type ofceramide compound a glycoceramide or a short-chain ceramide. In anotherembodiment, the ceramide compound in the composition of the inventionmay be a mixture of a glycoceramide and a short-chain ceramide.

[0034] Next to the free sphingoid base and the ceramide, other activeingredients may be present in the composition according to theinvention. For instance, the combination of a free sphingoid base and aceramide may advantageously be applied in combination with aconventional antiinflammatory and/or antimicrobial agent, where saidconventional antiinflammatory and/or antimicrobial agent may be appliedin substantially lower concentrations than typically used, because ofthe activity of the free sphingoid base.

[0035] An example of a conventionally used antiinflammatory agent is acorticosteroid.

[0036] Other active ingredients which may advantageously be applied inthe compositions according to the invention, in combination with a freesphingoid base and a ceramide, are agents which have an effect on skinappearance.

[0037] For instance, yeast β-glucan may be applied in the compositionaccording to the invention to reduce UV-induced erythema. Skin-peelingagents, like α-hydroxyacids, urea, salicylic acid or proteases, may beapplied in the composition according to the invention to improvedesquamation and/or decrease roughness of the skin. Retinoids may beapplied in the composition according to the invention to stimulate themitotic and metabolic activity of epidermal cells. Vitamin C and/or Emay be applied in the composition of the invention for their antioxidantactivity on skin components, which favours their application as, forinstance, antiageing agents.

[0038] The free sphingoid base as well as the ceramide may be present inthe composition according to the invention in a concentration of 0.001to 10%, preferably in a concentration of 0.005 to 5%, more preferably ina concentration of 0.01-2%, most preferably in a concentration of0.02-1.0%.

[0039] The ratio of free sphingoid base to ceramide in the compositionaccording to the invention may lie within a range of 1 to 10 to 10 to 1.Preferably, said ratio may vary from about 1 to 5 to about 5 to 1. Morepreferably, said ratio may vary from about 1 to 5 to about 1 to 1.

[0040] Next to the active ingredients, the topical preparations of theinvention further include the usual components.

[0041] The composition comprises a vehicle to enable the activeingredients to be conveyed to the skin.

[0042] The vehicle enables proper application on skin and/or hair, toprovide both a dermatological as well as a cosmetic treatment. Thecomposition may comprise a solid, semi-solid or liquid cosmeticallyand/or physiologically acceptable vehicle. The nature of the vehiclewill depend upon the method chosen for topical administration of thecomposition. Vehicles other than water can include liquid or solidemollients, solvents, humectants, thickeners, powders, surfactants,which are also sometimes designated as emulsifiers, solubilizers,propellants and other active ingredients.

[0043] Emollients can be classified under such general chemicalcategories as (fatty acid) esters, fatty acids, (fatty) alcohols,polyols, (natural) waxes, natural oils, silicone oils, both volatile andnon-volatile and hydrocarbons such as mineral oil, petroleum jelly,vaseline, squalens and (iso)paraffin.

[0044] Surfactants including emulsifiers may be cationic, nonionic,anionic or amphoteric in nature. A single type of surfactant and/orcombinations of surfactants may be employed.

[0045] Illustrative for nonionic surfactants are alkoxylated compoundsbased upon fatty alcohols, fatty acids and sorbitan.

[0046] Anionic-type surfactants may include fatty acid soaps, laurylsulphate salts, lauryl ether sulphate salts, alkyl benzene sulphonates,alkyl acid phosphates.

[0047] Amphoteric surfactants include materials as dialkylamine oxideand various types of betaines, such as cocoamido propyl betaine.

[0048] Cationic surfactants comprise quaternary ammonium compounds(Quats) such as cetyl trimethyl ammonium chloride or bromide.

[0049] A special class of surfactants are silicone surfactants, whichare high molecular weight polymers of dimethyl polysiloxane withpolyoxyethylene and/or polyoxypropylene side chains having a molecularweight of 10,000 to 50,000 D.

[0050] In general, surfactants used for the preparation of emulsionsinclude emulsifiers comprising compounds having a HLB(hydrophilic/lipophilic balance) value which is in the lower as well asin the higher ranges, i.e. compounds which are able to form awater-in-oil as well as compounds which are able to form an oil-in-wateremulsion, respectively. Typically, if a water-in-oil emulsion isrequired, the HLB value of the emulsifier or mixture of emulsifiersvaries between about 1 and 7. For an oil-in-water emulsion, said HLBvalue is higher than about 7.

[0051] Specific emulsifiers comprise emulsifiers which are able to forma lamellar phase (liquid crystalline or gel phase). Lamellar phases areformed at the oil-water interphase of an oil-in-water emulsion anddirectly incorporate the free sphingoid base and the ceramide. Examplesof such specific emulsifiers are:

[0052] 1. Fatty acids+neutralized fatty acids:

[0053] e.g. stearic acid, isostearic acid, etc.

[0054] 2. Glyceryl mono-fatty acid ester+neutralized fatty acids:

[0055] glyceryl stearate SE, glyceryl oleate SE

[0056] 3. Glyceryl mono-fatty acid ester+ethoxylated fattyalcohols/esters:

[0057] glyceryl stearate+Ceteareth-20+various

[0058] glyceryl stearate+PEG-20 glyceryl stearate

[0059] 4. High-ethoxylated fatty alcohols+low-ethoxylated fatty alcohols(+polar emollients):

[0060] Steareth-2+Steareth-21 (+PPG-15 stearyl ether/fatty alcohol)

[0061] Ceteareth-6+Ceteareth-25

[0062] Cetearyl Alcohol+Ceteareth-20

[0063] 5. Various polyglyceryl esters+combinations:

[0064] polyglyceryl-3-methyl glucose distearate.

[0065] polyglyceryl-10 pentastearate+behenyl alcohol+sodium stearoyllactylate

[0066] polyglyceryl-2 isostearate (or resp. di/tri/tetra isostearate)

[0067] polyglyceryl-3 diisostearate

[0068] 6. Various other sugar-esters:

[0069] Cetearylglucoside+Cetearyl alcohol

[0070] methyl glucose sesquistearate+PEG-20 methyl glucosesesquistearate

[0071] Sorbitan stearate+sucrose cocoate

[0072] Sorbitan stearate+polysorbate 60

[0073] sucrose esters (laurate/palmitate/stearate/oleate/isostearate)

[0074] 7. Lecithins and other Phospholipids:

[0075] lecithin

[0076] Propellants include propane, butane, isobutane, dimethyl ether,chlorofluoroalkanes, carbon dioxide, nitrous oxide.

[0077] Solvents include ethyl alcohol, methylene chloride, isopropanol,ethyl ethers such as ethoxyethanol and butoxyethanol, acetone,tetrahydrofuran, dimethyl formamide, DMSO, propylene glycol, butyleneglycol.

[0078] Humectants include proteins and protein hydrolysates, aminoacids, sorbitol, glycerin, sorbitol, glycols preferably PEG 200-4000 andother polyols.

[0079] Thickeners include cross linked polyacrylates, silicone gums andpolysaccharide gums such as xanthan, carrageenan, gelatin, pection andlocust beans gum, hyaluronic acid and carboxylic group-containingpolymers

[0080] Powders include chalk, talc, starch, kaolin, clays, silicates,carboxyvinyl polymers.

[0081] Other active ingredients include:

[0082] anti-oxidants like butyl hydroxy toluene, ascorbic acid andsalts, EDTA, hydroquinone, tocopherols, gallates;

[0083] preservatives like para-hydroxy benzoate esters, sorbic acid,EDTA, quaterniums, benzoic acid, imidazolidinyl urea, (benzyl)alcohol;

[0084] enzyme regulators like vitamins and other co-factors;

[0085] penetration enhancers like mono- or di-esters of C2 to C10alcohols and C8 to C18 fatty acids, propanols, urea, sugar esters, POEesters or ethers of fatty acids and/or alcohols, butan-1,4 diol,tetrahydrofuran, salicylate salts, pyrrolidones,N-alkyl-aza-cycloheptanones, oleic acid, linoleic acid;

[0086] sunscreens, blocking UV light, like PABA's, cinnamate andsalicylate derivatives;

[0087] other actives like coloring agents or perfumes.

[0088] The combination of the said components can account for 5 to 99%of the composition.

[0089] The positive and beneficial effects of the compositions accordingto the invention on affected skin areas are various and are summarizedas follows: a reduction of redness, dryness, roughness and/or scaling ofthe skin, a reduction of pruritis, a reduction of skin lesions, animprovement in healing of small wounds, a decrease of inflammatorysymptoms in affected areas, a decrease of an infectious state of theskin in affected areas.

[0090] Examples of skin conditions which benefit from topicalapplication of a composition according to the invention are psoriasis,atopic dermatitis, irritant and allergic contact dermatitis, seborrheicand sebostatic dermatitis, photodermatitis (UV-induced erythema), acne,ichthyosis, xerosis, aged skin. The skin infections which benefit fromtopical application of the compositions of the invention includebacterial, fungal, yeast and viral infections. For example dandruff,impetigo, Pityriasis vesicolor, Tinea corporis, Rosacea, Herpes,venereal diseases.

[0091] For specific skin conditions, i.e. wounds, burns, scalds, acombination of a free sphingoid base and a cerebroside is preferred,since cerebrosides (contrary to ceramides) tend to stimulate theproliferation of keratinocytes.

[0092] On the other hand, for skin diseases where, next to an impairedbarrier function and skin infections, hyperproliferation, reduceddifferentation and reduced desquamation are general symptoms, theinclusion of ceramides with a short-chain acyl group may beadvantageous. These short-chain ceramides will have the additionaleffect that they are cell-permeable and known to reduce proliferation,increase differentiation and increase desquamation.

[0093] The present invention is exemplified by several formulations andby an efficacy study using test persons with different skin disorders.Furthermore, the antiimflammatory activity of a free sphingoid base isdemonstrated.

EXAMPLE 1 Formulations Comprising Phytosphingosine and Several Ceramides

[0094] Below, several examples of suitable formulations according to theinvention are given.

[0095] The ceramides and the free sphingoid base used in theseformulations are the following:

[0096] Ceramide III: N-stearoyl-phytosphingosine

[0097] Ceramide IIIB: N-oleoyl-phytosphingosine

[0098] Ceramide VI: N-alpha-hydroxystearoyl-phytosphingosine

[0099] Phytosphingosine: 2-amino-octadecane-1,3,4-triol

[0100] Phytoceramide I: N-stearoyloxyheptacosanoyl-phytosphingosineWaterless Barrier Cream I comprising Ceramide III, Ceramide VI andPhytosphingosine INCI-name Trade name Percentage (% w/w) Hydrogenatedlecithin 4.0 Glycerin 48.0 Butylene glycol 18.0 Jojoba oil 5.0 Propyleneglycol Miglyol 840 (Huls) 10.0 dicaprylate/dicaprate Isocetyl alcoholEutanol G16 (Henkel) 3.0 Tocopheryl acetate 5.0 Dimethicone copolyol 5.0eicosonate Ceramide 3 Ceramide III 0.5 (Cosmoferm) Ceramide IIIB 0.5(Cosmoferm) Ceramide 6 Ceramide VI 0.5 (Cosmoferm) PhytosphingosinePhytosphingosine 0.5 (Cosmoferm) Waterless Barrier Creams II and IIIcomprising Ceramide III, Ceramide VI and Phytosphingosine, andadditionally cholesterol and stearic acid INCI-name Trade namePercentage (% w/w) Hydrogenated Lecithin Amisol 905 (Lucas 4.0 4.0Meyer) Glycerin 30.0 24.0 Butylene glycol 20.0 20.0 Glycerophospholipids Biophilic S (Lucas 1.5 1.5 Meyer) Jojoba oil 5.0 5.0Paraffin 10.0 10.0 Propylene glycol Myritol PC (Henkel) 10.0 10.0dicaprylate/ dicaprate Isocetyl alcohol Eutanol G16 (Henkel) 8.0 8.0Hydrogenated Cremeol HF52 (Aarhus) 5.0 5.0 vegetable oil Tocopherylacetate BASF 5.0 5.0 Ceramide 3 Ceramide III 0.25 1.25 (Cosmoferm)Ceramide IIIB 0.25 1.25 (Cosmoferm) Ceramide 6 Ceramide VI 0.25 1.25(Cosmoferm) Phytosphingosine Phytosphingosine 0.25 1.25 (Cosmoferm)Cholesterol 0.25 1.25 Stearic acid Unichema 0.25 1.25 Barrier Cream IVcomprising Phytoceramide I, Ceramide III and IIIB, Ceramide VI,Phytosphingosine and Acetyl-phytosphingosine INCI-name Trade namePercentage (% w/w) Lecithin (and) C12-16 Biophilic S 2.0 alcohols (and)palmitic (Lucas Meyers) acid Polyglyceryl-3 Methyl- Tego Care 450 2.0glucose Distearate (Goldschmidt) Cetearyl alcohol Lanette O 1.0 (Henkel)Propylene glycol Myritol PC 10.0 dicaprylate/dicaprate (Henkel) Isocetylalcohol Eutanol G16 10.0 (Henkel) Rice Bran oil 5.0 Tocopheryl acetateBASF 2.0 Ceramide 3 Ceramide III 0.5 (Cosmoferm Ceramide IIIB 0.5(Cosmoferm) Ceramide 6 Ceramide VI 0.5 (Cosmoferm) PhytosphingosinePhytosphingosine 0.5 (Cosmoferm) Ceramide 1 Phytoceramide 1 0.1(Cosmoferm) Acetyl-Phytosphingosine C2-Ceramide 0.1 (Cosmoferm) Stearicacid 0.5 Cholesterol 0.5 Butylene glycol 6.0 Mixed parabens in Phenonip0.6 Phenoxyethanol Water 64.4 Liposomal formulation comprising CeramideIII, Ceramide IIIB, Ceramide VI and phytosphingosine, and additionallycholesterol and linoleic acid INCI-name Trade name Percentage (% w/w)Sodium lauroyl lactylate 9.0 Tocopherol acetate 0.01 Carbomer 0.3Ceramide 3 Ceramide III 0.2 (Cosmoferm Ceramide IIIB 0.2 (Cosmoferm)Ceramide 6 Ceramide VI 0.1 (Cosmoferm) Phytosphingosine Phytosphingosine0.5 (Cosmoferm) Linoleic acid 0.25 Cholesterol 0.25 Water 89.2

EXAMPLE 2 Efficacy Evaluation of Barrier Cream I

[0101] To test the efficacy of a composition comprising a free sphingoidbase and a ceramide, barrier cream I was applied daily by several testpersons suffering from various skin disorders. The results are indicatedin Table 1. It is clear that the use of a barrier cream according to theinvention results in a significant improvement of the affected skinareas. TABLE 1 Person Condition Application Effect 1 Psoriatic 8 weeksStrong improvement; lesions on right 1* per day lesions have practicallyleg disappeared; small wounds appear to heal faster 2 Dry xerotic 3weeks Clear improvement; skin is skin, in 1* per day less scaly and redparticular on cheeks 3 Ichtyosis over 8 weeks Improvement is visible; nowhole body 1* per day, itching feeling like with only on the urea creamface 4 Atopic skin 4 weeks Improvement; comparable to 1* per daycorticosteroid cream 5 Psoriatic 4 weeks Improvement; lesions lesions onthe 1* per day return upon withdrawal elbow

EXAMPLE 3 Effect of the Free Sphingoid Base Phytosphingosine on theSecretion of Cytokines as a Marker for Antiinflammatory Activity

[0102] Principle:

[0103] The effect of phytosphingosine was assessed ex vivo on excisedhuman skin explants.

[0104] The explant was exposed to UV-B rays as a physical,proinflammatory stress.

[0105] The antiinflammatory effect of phytosphingosine was evaluated bymeasurement of the amount of the cytokine IL-1α secreted in theincubation medium of the skin explants.

[0106] Protocol:

[0107] Preparation of the human skin explants obtained after plasticsurgery using standard techniques.

[0108] Application of the test product: resp. 0% (Placebo), 0.2 and 0.5%phytosphingosine (PS) in Propylene glycol:Ethanol (60:40). Dexamethasone(1 μM) was used as the reference product.

[0109] The products were applied before and after irradiation (˜2mg/cm²)

[0110] IL-1α secretion was measured in the incubation medium of the skinexplants, using a standard ELISA technique.

[0111] Each experimental condition was performed in triplicate.

[0112] Results: Before After UV-B UV-B Dexamethasone Placebo 0.2% PS0.5% PS 48 205 116* 165 82* 92*

1. A composition for topical use comprising a combination of a freesphingoid base and a ceramide, said free sphingoid base having a generalstructure according to Formula 1:

wherein: A is CH₂—CH₂, CH═CH or C(H)OH—CH₂, and R is a straight chain orbranched alkyl group having 10 to 22 carbon atoms which may optionallycontain one or more double bonds and/or may optionally be substitutedwith one or more hydroxyl groups, preferably is a straight chain alkylgroup having 12 to 18 carbon atoms, more preferably is a straight chainalkyl group having 13 carbon atoms, and said ceramide having a generalstructure according to Formula 2:

wherein: A and R are defined as above, and R′ is a straight chain orbranched alkyl group having 13 to 55 carbon atoms, preferably 15 to 50carbon atoms, more preferably 17 to 44 carbon atoms; the alkyl chain mayoptionally be interrupted by an oxygen atom or by an internal estergroup; may optionally contain one or more double bonds; and mayoptionally be substituted with one or more hydroxyl groups.
 2. Thecomposition of claim 1, wherein the free sphingoid base is selected fromthe group of sphingosine, sphinganine and phytosphingosine.
 3. Thecomposition of claim 1 or 2, wherein the ceramide is a ceramide whichcorresponds in stereochemical configuration to a ceramide isolatablefrom mammalian skin.
 4. The composition of any one of the claims 1-3,wherein the ceramide is a mixture of two or more different ceramides. 5.The composition of any one of the claims 1-4, wherein the compositionfurther comprises one or more additional skin lipid compounds.
 6. Thecomposition of any one of the claims 1-5, wherein a ceramide is presentin addition to or instead of the ceramide according to Formula 2 whichis selected from the group of glycoceramides and short chain ceramides.7. The composition of claim 1 which is a dermatological composition. 8.The composition of claim 1 which is a cosmetic composition.
 9. Use ofthe composition of claim 1 for the manufacture of a topical compositionfor the treatment of a skin condition associated with an impairedbarrier function.
 10. Use according to claim 9, wherein said skincondition is further associated with a condition selected from the groupconsisting of a deranged regulation of cell growth and differentiation,an imflammatory condition or an infectious state.
 11. A method for thetreatment of a skin condition associated with an impaired barrierfunction comprising the topical application of a composition accordingto claim
 1. 12. The method of claim 11, wherein said skin condition isfurther associated with a condition selected from the group consistingof a deranged regulation of cell growth and differentiation, animflammatory condition or an infectious state.
 13. The method of claim12 which is a non-therapeutical method.